Decrease in urethral pressure following repeated cough efforts: A new concept for pathophysiology of stress urinary incontinence

Introduction & hypothesis: This is an experimental pre-clinical study testing for the applicability of autologous skeletal muscle derived cells as a seeded sling for the treatment of Stress urinary incontinence in canine model. Methods: 10 Mongrel dogs: In 4, skeletal muscle biopsy was harvested from Biceps Femoris. 1 month later, incontinence was induced in 8 dogs through surgical disruption of the pubourethral ligaments. Muscle biopsy was incubated in medium and after expansion for 8 weeks, Muscle derived cells were collected. Polyglycolic acid scaffold was immersed in culture medium, coated with matrigel and cells were seeded. The sling was placed suburethral in 8 dogs; 2 of which were cell-seeded and 4 had the scaffold only. Urethral pressure measurement was done at baseline and 2 weeks after insertion of the sling. The urethra with its surrounding was harvested 4 weeks after sling insertion for histopathology. 2 dogs were considered as control, in which no urethrolysis or insertion of slings was carried out. Results: Urethral pressure shows increase of maximum urethral pressure during static measurement in all dogs with a scaffold inserted. The increase ranged from 5-40 centimeter water (Median: 23 cmH20). Histopathology shows significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffold, as demonstrated by Desmin. This was maximum in dogs numbers 1and 2. This was not the case in the 4 dogs that had Polyglycolic acid sling only. Conclusion: The use of skeletal muscle-seeded scaffold is a practical technique with preserved integrity of histological differentiation in canine model at short term.

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Therapeutic potential of muscle growth promoters in a stress urinary incontinence model

AJP Renal Physiology ◽

10.1152/ajprenal.00122.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. F436-F446

Author(s):

Jun Yang ◽

Brian Balog ◽

Kangli Deng ◽

Brett Hanzlicek ◽

Anna Rietsch ◽

...

Keyword(s):

Urinary Incontinence ◽

Stress Urinary Incontinence ◽

Pelvic Floor ◽

Therapeutic Potential ◽

Muscle Growth ◽

Pelvic Floor Muscles ◽

Urethral Pressure ◽

Urethral Sphincter ◽

External Urethral Sphincter ◽

Muscle Recovery

Weakness of urinary sphincter and pelvic floor muscles can cause insufficient urethral closure and lead to stress urinary incontinence. Bimagrumab is a novel myostatin inhibitor that blocks activin type II receptors, inducing skeletal muscle hypertrophy and attenuating muscle weakness. β2-Adrenergic agonists, such as 5-hydroxybenzothiazolone derivative (5-HOB) and clenbuterol, can enhance muscle growth. We hypothesized that promoting muscle growth would increase leak point pressure (LPP) by facilitating muscle recovery in a dual-injury (DI) stress urinary incontinence model. Rats underwent pudendal nerve crush (PNC) followed by vaginal distension (VD). One week after injury, each rat began subcutaneous (0.3 mL/rat) treatment daily in a blinded fashion with either bimagrumab (DI + Bim), clenbuterol (DI + Clen), 5-HOB (DI + 5-HOB), or PBS (DI + PBS). Sham-injured rats underwent sham PNC + VD and received PBS (sham + PBS). After 2 wk of treatment, rats were anesthetized for LPP and external urethral sphincter electromyography recordings. Hindlimb skeletal muscles and pelvic floor muscles were dissected and stained. At the end of 2 wk of treatment, all three treatment groups had a significant increase in body weight and individual muscle weight compared with both sham-treated and sham-injured rats. LPP in DI + Bim rats was significantly higher than LPP of DI + PBS and DI + Clen rats. There were more consistent urethral striated muscle fibers, elastin fibers in the urethra, and pelvic muscle recovery in DI + Bim rats compared with DI + PBS rats. In conclusion, bimagrumab was the most effective for increasing urethral pressure and continence by promoting injured external urethral sphincter and pelvic floor muscle recovery.

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